Safety and tolerability of a 2009 trivalent inactivated split‐virion influenza vaccine in infants, children and adolescents

Abstract

ObjectiveTo evaluate the safety of CSL's split‐virion inactivated trivalent 2009 Southern Hemisphere formulation influenza vaccine (TIV) in children.MethodsWe enrolled 1992 healthy children into three groups: Cohorts A, ≥6 months to <3 years; B, ≥3 years to <9 years; and C, ≥9 years to <18 years. Children received one or two doses of 0·25 ml (22·5 μg haemagglutinin) or 0·5 ml (45 μg) TIV, depending on age and prior vaccination history. We collected post‐vaccination solicited adverse event (AE) data (days 0–6), including fever (temperature: ≥37·5°C axilla, ≥38·0°C oral), unsolicited AEs (days 0–29) and serious AEs (SAEs) and new‐onset chronic illnesses (NOCIs; to day 180 after last vaccination).ResultsAt least one solicited AE was reported by 80%/78%/78% of children in Cohorts A, B and C, respectively. Systemic AEs were more common among Cohort A (72% of participants), and local AEs were more common among Cohort C (71% of participants). Fever was more common in younger cohorts, in influenza vaccine‐naïve children (29% of Cohort A receiving their first dose), and following first compared with second doses. Severe fever following a first dose prevented 20 participants receiving their second scheduled vaccine dose. A 7‐month‐old participant had a single uncomplicated febrile convulsion on the day of vaccination.ConclusionsNearly 80% of subjects reported at least one solicited AE following immunization. Fever prevalence was highest in vaccine‐naïve Cohort A participants, similar to other paediatric studies using CSL vaccine. Further research to understand fever‐related AEs in children following CSL's TIV is recommended.

Systematic review of fever, febrile convulsions and serious adverse events following administration of inactivated trivalent influenza vaccines in children

“…Of the 4,372 studies initially identified (Figure), 18 RCTs [22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39], 14 non-randomised clinical trials [40][41][42][43][44][45][46][47][48][49][50][51][52][53], and six observational studies [54][55][56][57][58][59] were eligible for inclusion. The clinical trial registry search yielded 12 additional relevant studies (five RCTs and seven nonrandomised trials).…”

“…Two studies [48,52] were follow-on studies from previous RCTs. Most used within-study age cohorts for comparison and/or had no control group [40,42,[44][45][46][47]49,50,53]. For fever meta-analysis, we used five studies with fever defined as ≥ 38 °C [40,41,48,49,52] and two [47,53] where fever was ≥ 37.5 °C axillary or ≥ 38 °C orally (still meeting the Brighton Collaboration criteria [11]).…”

“…None of these RCTs had a high risk of bias. Analysis of five nonrandomised clinical trials [40,41,47,49,53] provided higher first-dose fever estimates of 17.7% (95% CI: 11.3-25.2), largely due to the inclusion of two studies of bioCSL vaccines [47,53] that reported higher rates of post-vaccination fever. Rates after second doses are listed in Table 3 and Table 4.…”

The manufacturing process should remain the focus for severe febrile reactions in children administered an Australian inactivated influenza vaccine during 2010

“…However, CSL's previous paediatric studies with their own vaccines, produced before the 2010 SH TIV, whilst not being associated with a high level of FS, showed concerning levels of fever, a necessary precursor of FS. Two uncontrolled trials conducted in 2005–2006 and 2009 documented fever rates in children aged 6–35 months of up to 39·5% and 28·6%, respectively 14, 15. These studies also documented FS, but only one in each study, both occurring on the day of vaccination among 19714 and 71015 vaccinees, respectively.…”

“…Neither study involved vaccines containing B/Brisbane/60/2008 or H1N1 A/California/7/2009 strains. B/Florida/4/2006 strain, which induced raised cytokine levels but to a lesser degree,3 was used in one study 15…”